Pharmacokinetic Study of Milrinone in Babies With Persistent Pulmonary Hypertension of the Newborn

This study has been terminated.
(Inadequate enrollment)
Sponsor:
Collaborators:
University of Pennsylvania
Bedford Pharmaceuticals
American Medical Association
Thrasher Research Fund
Information provided by (Responsible Party):
Haresh Kirpalani, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01088997
First received: March 12, 2010
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

The purpose of this pilot study is to determine a safe dose of milrinone to use in a larger study of babies with persistent pulmonary hypertension of the newborn (PPHN).


Condition Intervention
Persistent Pulmonary Hypertension of Newborn (PPHN)
Drug: milrinone lactate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Milrinone Pharmacokinetics and Pharmacodynamics in Newborns With Persistent Pulmonary Hypertension of the Newborn - a Pilot Study to Enable a Randomized Trial of Intervention

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Pharmacokinetic profile of milrinone in newborns with PPHN [ Time Frame: according to weight (see below) ] [ Designated as safety issue: No ]
    For infants <3 kg, samples will be collected at end of bolus, 15min prior to end of infusion (EOI), and after EOI at 20min, 1hr, 2hr, 6hr, & 12 hr. For infants >3 kg, samples will be collected at end of bolus, 6 hours after start of infusion, 15min prior to end of infusion (EOI), and after EOI at 30min, 1hr, 3hr, 9hr, & 15 hr. Samples will be stored at -70C and milrinone plasma concentrations measured by modification of a high-pressure liquid chromatography assay in laboratory of Clinical Pharmacology and Therapeutics at CHOP.


Secondary Outcome Measures:
  • Oxygenation index [ Time Frame: every 6 hours for 48 hours ] [ Designated as safety issue: No ]
    Oxygenation index (mean airway pressure*FiO2/PaO2) will be calculated every 6 hours.

  • Echocardiographic signs of pulmonary hypertension [ Time Frame: 12-24 hours ] [ Designated as safety issue: No ]
    An echocardiogram obtained while on milrinone will look for improvements in parameters associated with pulmonary hypertension. Parameters measured will be: myocardial performance index (MPI) of LV and RV, cardiac output of LV, tricuspid regurgitation (trivial, mild, moderate, severe), RV systolic pressure, mitral regurgitation (trivial, mild, moderate, severe), presence or absence of patent foramen ovale (PFO) with peak and mean pressure gradient, and presence or absence of patent ductus arteriosus (PDA) with peak and mean pressure gradient.

  • Safety profile [ Time Frame: 24-48 hours ] [ Designated as safety issue: Yes ]
    Safety analysis will be performed as follows: blood pressure will be monitored hourly for 48 hours, platelet count will be recorded daily, cardiac rhythm will be monitored continuously for 48 hours, renal function will be recorded daily, and liver transaminases will be recorded within a week. All adverse events will be included in the safety analysis. Interim safety analyses will be performed after 1/3 and 2/3 of subjects have been enrolled. A data safety monitoring committee will meet monthly to discuss adverse events and interim analyses.


Enrollment: 10
Study Start Date: June 2010
Estimated Study Completion Date: May 2015
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: high dose
50 mcg/kg load followed by 0.5 mcg/kg/min infusion
Drug: milrinone lactate
Milrinone lactate will be given as an IV infusion for 24 hours.
Other Name: Milrinone lactate
Experimental: low dose
20 mcg/kg load followed by 0.2 mcg/kg/min infusion
Drug: milrinone lactate
Milrinone lactate will be given as an IV infusion for 24 hours.
Other Name: Milrinone lactate

Detailed Description:

Persistent pulmonary hypertension of the newborn (PPHN) is a condition in which the pulmonary vasculature fails to relax after birth resulting in severe hypoxemia. This condition has a high rate of mortality and morbidity. The current standard of care is treatment with inhaled nitric oxide (iNO). However, for many babies this treatment does not provide sufficient improvement in oxygenation.

In this study, subjects already receiving nitric oxide will be randomized to one of two dosing regimens of milrinone. They will receive milrinone IV for 24 hours and will be monitored for 24 hours afterwards. During this time, milrinone assays will be performed by blood sampling. Echocardiograms will also be performed to explore the pharmacodynamics of milrinone. Safety monitoring will be performed.

  Eligibility

Ages Eligible for Study:   up to 10 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Gestational age > 34 weeks
  • Post-natal age < 10 days
  • Hypoxemia defined by: Oxygenation Index (OI) >15 (Mean Airway Pressure x Fraction of Inspired Oxygen x 100 /PaO2) as drawn from two post-ductal arterial blood gas samples (in-dwelling arterial catheter) taken at least 15 minutes apart. OR mechanically ventilated and with >75% FiO2 for >6 hours while on iNO
  • Absence of congenital heart disease based on a two-dimensional echocardiogram and/or clinical assessment
  • An in-dwelling arterial catheter to facilitate painless sampling
  • Currently on iNO or plan to start iNO before enrollment

Exclusion Criteria:

  • Lethal non-cardiac congenital anomalies including diaphragmatic hernia
  • Clinically apparent bleeding; thrombocytopenia <30,000 or other laboratory evidence of coagulopathy
  • Currently on ECMO or plan to initiate ECMO within 2 hours of enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088997

Locations
United States, Michigan
Children's Hospital of Michigan/Hutzel Women's Hospital
Detroit, Michigan, United States, 48201-2196
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Haresh Kirpalani
University of Pennsylvania
Bedford Pharmaceuticals
American Medical Association
Thrasher Research Fund
Investigators
Principal Investigator: Haresh Kirpalani, MD Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Haresh Kirpalani, Professor of Pediatrics, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01088997     History of Changes
Other Study ID Numbers: 09-007384
Study First Received: March 12, 2010
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital of Philadelphia:
Persistent pulmonary hypertension of newborn
PPHN
Persistent pulmonary hypertension
pulmonary hypertension
pulmonary hypertension of newborn

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases
Milrinone
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014